CH17 - Central Nervous System Pathology Flashcards Preview

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Flashcards in CH17 - Central Nervous System Pathology Deck (315):
1

What are the developmental anomolies?

1) neural tube defects 2) cerebral aqueduct stenosis 3) Dandy Walker Malformation 4) Arnold Chiari Malformation

2

What do neural tube defects arise from?

They arise from incomplete closure of the neural tube

3

What happens to the neural plate early in gestation?

It invaginates to form the neural tube, which runs along the cranial caudal axis of the embryo

4

Regarding the neural plate, what forms the central nervous system?

The wall of the neural tube forms central nervous system tissue,

5

In the neural tube, what does the hollow lumen form?

the ventricles and spinal cord canal, and the neural crest forms the peripheral nervous system.

6

What are neural tube defects associated with?

low folate levels prior to conception

7

When are neural tube defects detected?

during prenatal care by elevated alpha-fetoprotein (AFP) levels in the amniotic fluid and maternal blood

8

What is anencephaly?

it is the absence of the skull and brain (disruption of the cranial end of the neural tube)

9

What does anencephaly lead to?

a frog like appearance of the fetus

10

What does anencephaly result in?

maternal polyhydramnios since fetal swallowing of amniotic fluid is impaired

11

What is spina bifida?

It is failure of the posterior vertebral arch to close, resulting in a vertebral defect (disruption of the caudal end of the neural tube).

12

How does Spina bifida occulta present?

as a dimple or patch of hair overlying the vertebral defect.

13

How does Spina bifida present?

with cystic protrusion of the underlying tissue through the vertebral defect

14

What is a meningocele?

protrusion of meninges

15

What is meningomyelocele?

protrusion of meninges and spinal cord

16

What is cerebral aqueduct stenosis?

congenital stenosis of the channel that drains cerebrospinal fluid (CSF) from the 3rd ventricle into the 4th ventricle

17

What does cerebral aqueduct stenosis lead to?

accumulation of CSF in the ventricular space; most common cause of hydrocephalus in newborns

18

What is the most common cause of hydrocephalus in newborns?

Cerebral aqueduct stenosis

19

What produces the CSF?

It is produced by the choroid plexus lining the ventricles

20

Decribe the flow of CSF?

from the lateral ventricles into the 3rd ventricle via the interventricular foramen of Monro, Flows from the 3rd ventricle into the 4th ventricle via the cerebral aqueduct, Flows from the 4th ventricle into the subarachnoid space via the foramina of Magendie and Luschka

21

What is the cerebral aqueduct?

Allows for the flow from the 3rd ventricle into the 4th ventricle

22

What allows the CSF to flow from the 4th ventricle into the subarachnoid space?

Via the foramina of Magendie and Luschka

23

What is the foramen of monro?

Allows for the flow of CSF from the lateral ventricles into the 3rd ventricle

24

What does cerebral aqueduct stenosis present with?

enlarging head circumference due to dilation of the ventricles (cranial suture lines are not fused)

25

What is a dandy walker malformation?

Congenital failure of the cerebellar vermis to develop

26

How does a dandy walker malformation present?

as a massively dilated 4th ventricle (posterior fossa) with an absent cerebellum; often accompanied by hydrocephalus

27

What is an Arnold chiari malformation?

Congenital extension of cerebellar tonsils through the foramen magnum

28

What might Arnold Chiari malformation result in?

Obstruction of CSF flow can result in hydrocephalus

29

What might Arnold chiari malformation occur in association with?

meningomyelocele and syringomyelia

30

What are the spinal cord lesions?

Syringomyelia, poliomyelitis, Werdnig-Hoffmann disease, amyotrophic lateral sclerosis, Friedreich ataxia

31

What is syringomyelia?

Cystic degeneration of the spinal cord

32

What does syringomyelia arise with?

trauma or in association with an Arnold-Chiari malformation

33

Where does syringomyelia usually occur?

at C8-T1

34

How does syringomyelia present?

as sensory loss of pain and temperature with sparing of fine touch and position sense in the upper extremities (cape like distribution)

35

What is the presentation of syringomyelia due to?

involvement of the anterior white commissure of the spinothalamic tract with sparing of the dorsal column

36

What does syrinx expansion result in?

involvement of other spinal tracts leading to 1. Muscle atrophy and weakness with decreased muscle tone and impaired reflexes 2. Horner syndrome with ptosis (droopy eyelid), miosis (constricted pupil), and anhidrosis (decreased sweating)

37

Why does the syrinx expansion result in muscle atrophy and weakness with decreased muscle tone and impaired reflexes?

Its due to damage to lower motor neurons of the anterior horn

38

What is ptosis?

Droopy eyelid

39

What is miosis?

Constricted pupil

40

What is anhidrosis?

Decreased sweating

41

Why does the syrinx expansion lead to horner syndrome with ptosis (droopy eyelid), miosis (constricted pupil), and anhidrosis (decreased sweating)?

It?s due to disruption of the lateral horn of the hypothalamospinal tract

42

What is poliomyelitis?

Damage to the anterior motor horn due to poliovirus infection

43

How does poliomyelitis present?

with lower motor neuron signs?flaccid paralysis with muscle atrophy, fasciculations, weakness with decreased muscle tone, impaired reflexes, and negative Babinski sign (downgoing toes)

44

What is Werdnig-Hoffman disease?

It?s an inherited degeneration of the anterior motor horn and is autosomal recessive

45

How does Werdnig-Hoffman disease present?

as a floppy baby, death occurs within a few years after birth.

46

What is amyotrophic lateral sclerosis?

Degenerative disorder of upper and lower motor neurons of the corticospinal tract

47

In ALS, what does anterior motor horn degeneration lead to?

lower motor neuron signs?flaccid paralysis with muscle atrophy, fasciculations, weakness with decreased muscle tone, impaired reflexes, and negative Babinski sign.

48

In ALS what does lateral corticospinal tract degeneration lead to?

upper motor neuron signs ? spastic paralysis with hyperreflexia, increased muscle tone, and positive Babinski sign.

49

What is an early sign of ALS?

atrophy and weakness of hands is an early sign

50

What distinguishes ALS from syringomyelia?

Lack of sensory impairment

51

What are most cases of ALS?

they are sporadic, arising in middle age adults

52

What is present in some familial cases of ALS?

Zinc-copper superoxide dismutase mutation (SOD) is present in some familial cases; leads to free radical injury in neurons

53

What is Friedreich Ataxia?

Degenerative disorder of the cerebellum and spinal cord

54

What does degeneration of the cerebellum lead to?

ataxia

55

What does degeneration of multiple spinal cord tracts lead to?

loss of vibratory sense and proprioception, muscle weakness in the lower extremities, and loss of deep tendon reflexes

56

What is the cause of Friedreich Ataxia genetically?

Autosomal recessive; due to expansion of an unstable trinucleotide repeat (GAA) in the frataxin gene

57

What is frataxin?

it is essential for mitochondrial iron regulation; loss results in iron buildup with free radical damage.

58

How does Friedreich Ataxia present?

in early childhood; patients are wheelchair bound within a few years

59

What is Friedreich Ataxia associated with?

hypertrophic cardiomyopathy

60

What does the spinothalamic tract do?

Pain and temperature sensation

61

What is the first order neuron for the spinothalamic tract?

Peripheral nerves of posterior horn; cell body is in dorsal root ganglion.

62

What is the second order neuron for the spinothalamic tract?

It arises from posterior horn, immediately crosses over in anterior white commissure, and ascends via the spinothalamic tract to thalamus

63

What is the third order neuron for the spinothalamic tract?

thalamus to cortex

64

What is the Dorsal column-medial lemniscus responsible for?

pressure, touch, vibration, and proprioception

65

What are the first order neurons for the dorsal column-medial lemniscus?

Peripheral nerves to medulla via dorsal column; cell body is in dorsal root ganglion.

66

What is the second order neuron for the dorsal column-medial lemniscus?

Arises from medulla, crosses over, and ascends via the medial lemniscus to thalamus

67

What is the third order neuron for the dorsal column-medial lemniscus?

Thalamus to cortex

68

What is the lateral corticospinal tract responsible for?

voluntary movement

69

What are the first order neurons for the lateral corticospinal tract?

Pyramidal neurons in the cortex descend, cross over in medullary pyramids, and synapse on the anterior motor horn of the cord (upper motor neuron)

70

What is the second order neuron for the lateral corticospinal tract?

Arises from the anterior motor horn and synapses on muscle (lower motor neuron)

71

What are the third order neurons for the lateral corticospinal tract?

None

72

What is the hypothalamospinal tract responsible for?

sympathetic input of the face

73

What is the first order neuron for the hyothalamospinal tract?

It arises from the hypothalamus and synapses on the lateral horn at T1

74

What is the second order neuron for the hypothalamospinal tract?

It arises from lateral horn at T1 and synapses on the superior cervical ganglion (sympathetic)

75

What is the third order neuron for the hypothalamospinal tract?

Superior cervical ganglion to eyelids, pupil, and skin of face

76

What is meningitis?

inflammation of the leptomeninges

77

What do the meninges consist of?

three layers (dura, arachnoid, and pia) that lie between the brain and the skull,

78

What are the leptomeninges?

Pia and arachnoid together

79

What is meningitis most commonly due to?

an infectious agent

80

What are the infectious agents that cause meningitis?

1) Group B streptococci, E coli, and Listeria monocytogenes (neonates) 2) N meningitidis (children and teenagers). Streptococcus-pneumoniae (adults and elderly), and H influenza (non vaccinated infants) 3. Coxsackievirus (children; fecal-oral transmission) 4. Fungi (immunocompromised individuals)

81

What is the infectious agent causing meningitis for neonates?

Listeria monocytes

82

What is the infectious agent causing meningitis for children and teenagers?

N. Meningitidis

83

What is the infectious agent causing meningitis for adults and elderly?

Streptococcus-pneumoniae

84

What is the infectious agent causing meningitis for non vaccinated infants?

H. Influenzae

85

What is the infectious agent causing meningitis for children; fecal-oral transmission?

Coxsackievirus

86

What is the infectious agent causing meningitis for immunocomprimised individuals?

fungi

87

How does meningitis present?

With a classic triad of headache, nuchal rigidity (neck stiffness), and fever; photophobia, vomiting, and altered mental status may also be present,

88

How is the diagnosis for meningitis made?

it is made by lumbar puncture (sampling of CSF)

89

How is a lumbar puncture performed?

by placing a needle between L4 and L5 (level of the iliac crest). Spinal cord ends at L2, but subarachnoid space and cauda equina continue to S2.

90

What are the layers crossed by the lumbar puncture?

include skin, ligaments, epidural space, dura, and arachnoid.

91

What are the CSF findings in LP for bacterial meningitis?

neutrophils with low CSF glucose; positive gram stain and culture often identify the causative organism.

92

What are the CSF findings in LP for viral meningitis?

lymphocytes with normal CSF glucose

93

What are the CSF findings in LP for fungal meningitis?

lymphocytes with low CSF glucose

94

Complications are usually seen with what type of meningitis?

bacterial meningitis

95

What is involved in cerebrovascular disease?

Neurologic deficit due to cerebrovascular compromise; major cause of morbidity and mortality

96

What is cerebrovascular disease due to?

ischemia (85% of cases) or hemorrhage (15% of eases)

97

What are neurons dependent on and what are the susceptible to?

serum glucose as an essential energy source and are particularly susceptible to ischemia (undergo necrosis within 3 - 5 minutes).

98

What is global cerebral ischemia?

Global ischemia to the brain

99

What are the major etiologies for global cerebral ischemia?

1. Low perfusion (e.g., atherosclerosis) 2. Acute decrease in blood flow (e.g., cardiogenic shock) 3. Chronic hypoxia (e.g., anemia) 4. Repeated episodes of hypoglycemia (eg insulinoma)

100

What are the clinical features for global cerebral ischemia based on?

Its based on duration and magnitude of the insult.

101

What does mild global ischemia result in?

transient confusion with prompt recovery

102

What does severe global ischemia result in?

diffuse necrosis; survival leads to a vegetative state

103

What does moderate global ischemia lead to?

infarcts in watershed areas (eg area lying between regions fed by the anterior and middle cerebral artery) and damage to highly vulnerable regions

104

In moderate global ischemia, what are the vulnerable regions that may be damaged?

1) Pyramidal neurons of the cerebral cortex (layers 3, 5, and 6) 2) Pyramidal neurons of the hippocampus (temporal lobe) 3) Purkinje layer of the cerebellum

105

What does damage to the pyramidal neurons of the cerebral cortex (layers 3, 5, and 6) lead to?

laminar necrosis

106

What does damage to the pyramidal neurons of the hippocampus (temporal lobe) lead to?

Its important in long term memory

107

What does damage to the purkinje layer of the cerebellum lead to?

It integrates sensory perception with motor control

108

What is ischemic stroke?

Regional ischemia to the brain that results in focal neurologic deficits lasting > 24 hours

109

What happens in the symptoms last < 24 hours?

the event is termed a transient ischemic attack (TIA).

110

What are the subtypes for ischemic stroke?

They include thrombotic, embolic, and lacunar strokes.

111

What is the thrombotic stroke due to?

rupture of an atherosclerotic plaque

112

Where does atherosclerosis usually develop?

at branch points (e.g., bifurcation of internal carotid and middle cerebral artery in the circle of Willis).

113

What does atherosclerosis result in?

a pale infarct at the periphery of the cortex

114

What is an embolic stroke due to?

thromboemboli.

115

What is the most common source of emboli?

It is the left side of the heart (e.g., atrial fibrillation).

116

What does an embolic stroke usually involve?

the middle cerebral artery

117

What does the embolic stroke result in?

a hemorrhagic infarct at the periphery of the cortex

118

When does a lacunar stroke occur?

Its secondary to hyaline arteriolosclerosis, a complication of hypertension.

119

What vessels does lacunar stroke most commonly involve?

lenticulostriate vessels, resulting in small cystic areas of infarction

120

In a lacunar stroke, what does the nvolvement of the internal capsule lead to?

a pure motor stroke

121

In a lacunar stroke, what does the involvement of the thalamus lead to?

a pure sensory stroke.

122

What does ischemic stroke result in?

liquefactive necrosis,

123

What is an early microscopic finding (12 hours after infarction) for ischemic stroke?

Eosinophilic change in the cytoplasm of neurons (red neurons)

124

What happens 24 hours into an ischemic stroke?

coagulative necrosis

125

What happens in days 1-3 in an ischemic stroke?

infiltration by neutrophils

126

What happens in days 4-7 in an ischemic stroke?

microglial cells

127

What happens in weeks 2-3 in an ischemic stroke?

granulation tissue (weeks 2-3) then ensue

128

An ischemic stroke results in the formation of what?

a fluid-filled cystic space surrounded by gliosis

129

What is an intracerebral hemorrhage?

Bleeding into brain parenchyma

130

What is an intracerebral hemorrhage classically due to?

rupture of Charcot-Bouchard microaneurysms of the leniiculostriate vessels

131

What is intracerebral hemorrhage a complication of?

hypertension; treatment of hypertension reduces incidence by half.

132

What is the most common site for intracerebral hemorrhage?

Basal ganglia

133

What does intracerebral hemorrhage present as?

severe headache, nausea, vomiting, and eventual coma

134

What is subarachnoid hemorrhage?

Bleeding into the subarachnoid space

135

What does subarachnoid hemorrhage present as?

a sudden headache (worst headache of my life) with nuchal rigidity

136

What does the lumbar puncture shows in a subarachnoid hemorrhage?

xanthochromia (yellow hue due to bilirubin breakdown)

137

What is a subarachnoid hemorrhage most frequently due to?

(85%) rupture of a Berry aneurysm; other causes include AV malformations and an anti-coagulated state,

138

What are Berry aneurysms?

they are thin-walled saccular outpouching that lack a media layer, increasing the risk for rupture.

139

What are Berry aneurysms most frequently located?

in the anterior circle of Willis at branch points of the anterior communicating artery

140

What are Berry aneurysms associated with?

Marfan syndrome and autosomal dominant polycystic kidney disease

141

What is an epidural hematoma?

Collection of blood between the dura and the skull

142

What is an epidural hematoma classically due to?

fracture of the temporal bone with rupture of the middle meningeal artery; bleeding separates the dura from the skull.

143

In an epidural hematoma, what is seen on CT?

Lens-shaped lesion on CT

144

When do you see neurologic signs in an epidural hematoma?

Lucid interval may precede neurologic signs.

145

What is a lethal complication for an epidural hematoma?

Herniation is a lethal complication.

146

What is a subdural hematoma?

Collection of blood underneath the dura; blood covers the surface of the brain

147

What is the subdural hematoma due to?

tearing of bridging veins that lie between the dura and arachnoid; usually arises with trauma

148

What is seen on CT in subdural hematoma?

Crescent-shaped lesion on CT

149

What does subdural hematoma present with?

progressive neurologic signs

150

In whom is there an increased rate of occurrence for subdural hematoma?

in the elderly due to age-related cerebral atrophy, which stretches the veins

151

What is a lethal complication for subdural hematoma?

Herniation

152

What is herniation (brain)?

Displacement of brain tissue due to mass effect or increased intracranial pressure

153

What is tonsillar herniation?

It involves displacement of the cerebellar tonsils into the foramen magnum.

154

What might tonsillar herniation lead to?

the compression of the brain stem leads to cardiopulmonary arrest

155

What is subfalcine herniation?

It involves displacement of the cingulate gyrus under the falx cerebri.

156

What would subfalcine herniation lead to?

Compression of the anterior cerebral artery leads to infarction

157

What does uncal herniation involve?

the displacement of the temporal lobe uncus over the tentorium cerebelli.

158

Uncal herniation leads to what?

1) eye moving (down and out) and a dilated pupil. 2) infarction of the occipital lobe (contralateral homonymous hemianopsia). 3) Duret (brainstem) hemorrhage.

159

With an uncal herniation, why is there eye movement down and out and a dilated pupil?

Compression of cranial nerve III (oculomotor)

160

With an uncal herniation, why is there infarction of occipital lobe?

(contralateral homonymous hemianopsia) compression of posterior cerebral artery

161

With uncal herniation, why is there Duret (brainstem) hemorrhage?

Rupture of the paramedian artery leads to Duret (brainstem) hemorrhage.

162

What are the demyelinating disorders?

1) leukodystrophies 2) multiple sclerosis 3) subacute sclerosing panencephalitis 4) progressive multifocal leukoencephalopathy 5) Central pontine myelinolysis

163

What does myelin do?

it insulates axons, improving the speed and efficiency of conduction

164

What myelinates the central nervous system?

oligodendrocytes

165

What myelinates the peripheral nervous system?

Schwann cells

166

What are demyelinating disorders characterized by?

destruction of myelin or oligodendrocytes; axons are generally preserved.

167

What are leukodystrophies?

They are inherited mutations in enzymes necessary for production or maintenance of myelin

168

What are the leukodystrophies?

metachromatic leukodystrophy, Krabbe disease, adrenoleukodystrophy

169

What is metachromatic leukodystrophy due to?

a deficiency of arylsulfatase (autosomal recessive)

170

What is the most common leukodystrophy?

metachromatic leukodystrophy

171

What is metachromatic leukodystrophy?

Myelin cannot be degraded and accumulates in the lysosomes of oligodendrocytes (lysosomal storage disease)

172

What is Krabbe disease due to?

a deficiency of galactocerebroside beta-galactosidase (autosomal recessive) resulting in galactocerebroside to accumulate in macrophages.

173

What is adrenoleukodystrophy due to?

impaired addition of coenzyme A to long-chain fatty acids (X-linked defect).

174

What does adrenoleukodystrophy result in?

accumulation of fatty acids damages adrenal glands and white matter of the brain.

175

What is multiple sclerosis?

Autoimmune destruction of CNS myelin and oligodendrocytes

176

What is the most common chronic CNS disease of young adults (20-30 years of age)?

Multiple sclerosis

177

In whom is multiple sclerosis more commonly seen?

in women

178

What is multiple sclerosis associated with?

HLA-DR2

179

In what region is multiple sclerosis more commonly seen?

in regions away from the equator

180

What does multiple sclerosis present with?

relapsing neurologic deficits with periods of remission (multiple lesions in time and space)

181

What are the clinical features for multiple sclerosis?

1. Blurred vision in one eye (optic nerve) 2. Vertigo and scanning speech mimicking alcohol intoxication (brainstem) 3. Internuclear ophthalmoplegia (medial longitudinal fasciculus) 4. Hemiparesis or unilateral loss of sensation (cerebral white matter, usually periventricular) 5. Lower extremity loss of sensation or weakness (spinal cord) 6. Bowel, bladder, and sexual dysfunction (autonomic nervous system)

182

How is the diagnosis for multiple sclerosis made?

by MRI and lumbar puncture.

183

What does the MRI for multiple sclerosis reveal?

plaques (areas of white matter demyelination)

184

What does the lumbar puncture for multiple sclerosis show?

increased lymphocytes, increased immunoglobulins with oligoclonal IgG bands on high resolution electrophoresis, and myelin basic protein.

185

What does gross examination for multiple sclerosis show?

it shows gray-appearing plaques in the white matter

186

What is involved in the treatment of multiple sclerosis?

The acute attacks includes high-dose steroids and the long-term treatment with interferon beta slows progression of disease.

187

What is subacute sclerosing panencephalitis?

Progressive, debilitating encephalitis leading to death

188

What is subacute sclerosing panencephalitis due to?

slowly progressing, persistent infection of the brain by measles virus

189

For subacute sclerosing panencephalitis, when does the infection occur?

in infancy

190

For subacute sclerosing panencephalitis, when do the neurologic signs arise?

years later (during childhood)

191

What is subacute sclerosing panencephalitis characterized by?

viral inclusions within neurons (gray matter) and oligodendrocytes (white matter)

192

What is progressive multifocal leukoencephalopathy?

JC virus infection of oligodendrocytes (white matter)

193

What leads to reactivation of the latent virus?

Immunosuppression (e.g., AIDS or leukemia)

194

What does progressive multifocal leukoencephalopathy present with?

rapidly progressive neurologic signs (visual loss, weakness, dementia) leading to death

195

What is central pontine myelinolysis?

Focal demyelination of the pons (anterior brain stem)

196

What is central pontine myelinolysis due to?

Rapid intravenous correction of hyponatremia

197

In whom does central pontine myelinolysis occur?

in severely malnourished patients (e.g., alcoholics and patients with liver disease)

198

How does central pontine myelinolysis classically present?

as acute bilateral paralysis (locked in syndrome)

199

What are the dementia and degenerative disorders?

1) Alzheimer disease 2) vascular dementia 3) Pick disease 4) Parkinson Disease 5) Huntington Disease 6) Normal pressure hydrocephalus 7) spongiform encephalopathy

200

What are the dementia and degenerative disorders characterized by?

the loss of neurons within the gray matter

201

What are dementia and degenerative disorders often due to?

accumulation of protein which damages neurons

202

Degeneration of what leads to dementia?

the cortex

203

Degeneration of what leads to movement disorders?

the brainstem and basal ganglia

204

What is Alzheimer disease?

Degenerative disease of cortex; most common cause of dementia

205

What is the most common cause of dementia?

Alzheimer disease

206

What are the clinical features for Alzheimer disease?

1) Slow-onset memory loss (begins with short-term memory loss and progresses to long-term memory toss) and progressive disorientation 2) Loss of learned motor skills and language 3) Changes in behavior and personality 4) Patients become mute and bedridden; infection is a common cause of death. 5) Focal neurologic deficits are not seen in early disease.

207

In Alzheimer disease, what is the most common cause of death?

infection

208

What happens in most cases of Alzheimer disease

most cases (95%) are sporadic and seen in the elderly

209

The risk for developing Alzheimer disease increases with what?

age (doubles every 5 years after the age of 60)

210

What allele is associated with increased risk for Alzheimer disease?

Epsilon 4 allele of apolipoprotein E is associated with increased risk,

211

What allele is associated with decreased risk for Alzheimer disease?

Epsilon 2 allele is associated with decreased risk,

212

What is early-onset AD seen in?

it is seen in Familial cases and down syndrome

213

What are the Familial cases of early onset AD associated with?

presenilin 1 and presenilin 2 mutations

214

What is the relationship between down syndrome and early-onset AD?

commonly occurs by 40 years of age

215

What are the morphologic features for AD?

1) (diffuse) Cerebral atrophy with narrowing of the gyri, widening of the sulci, and dilation of the ventricles 2) Neuritic plaques 3) Neurofibrillary tangles 4) Loss of cholinergic neurons in the nucleus basalis of Meynert

216

What are Neuritic plaques?

Its an extracellular core comprised of Abeta (amyloid beta) amyloid with entangled neuritic processes

217

What is Abeta amyloid derived from?

amyloid precursor protein (APP), which is coded on chromosome 21. APP normally undergoes alpha cleavage; beta cleavage results in Abeta amyloid (cannot be broken down)

218

Where is amyloid precursor protein coded?

On chromosome 21

219

What normally happens to APP?

Normally undergoes alpha cleavage

220

What happens to APP in Alzheimer disease?

beta cleavage results in Abeta amyloid (cannot be broken down)

221

What is cerebral amyloid angiopathy?

Amyloid may also deposit around vessels, increasing the risk of hemorrhage resulting in cerebral amyloid angiopathy

222

What are neurofibrillary tangles?

They are intracellular aggregates of fibers composed of hyperphosphorylated tau protein

223

What is the Tau protein?

It is a microtubule-associated protein.

224

How is the diagnosis for Alzheimer disease made?

by clinical and pathological correlation. 1) Presumptive diagnosis is made clinically after excluding other causes, 2) Confirmed by histology at autopsy (when possible)

225

What is vascular dementia?

Multifocal infarction and injury due to hypertension, atherosclerosis, or vasculitis

226

What is the 2nd most common cause of dementia?

Vascular dementia

227

What is pick disease?

Degenerative disease of the frontal and temporal cortex; spares the parietal and occipital lobes

228

What is Pick disease characterized by?

round aggregates of tau protein (Pick bodies) in neurons of the cortex

229

What are the symptoms for Pick disease?

Behavioral and language symptoms arise early; eventually progresses to dementia

230

What is Parkinson disease?

It?s a degenerative loss of dopaminergic neurons in the substantia nigra of the basal ganglia

231

What is the nigrostriatal pathway?

It is a part of the basal ganglia that uses dopamine to initiate movement.

232

In what population is Parkinson?s disease common?

it?s a common disorder related to aging; seen in 2% of older adults

233

What is the etiology for Parkinson?s disease?

Unknown etiology; historically, rare cases were related to MPTP exposure (a contaminant in illicit drugs).

234

What are the clinical features for Parkinson?s disease?

TRAP ? 1) Tremor 2) Rigidity 3) akinesia/bradykinesia 4) Postural instability and shuffling gait

235

Describe the tremor seen in Parkinson?s disease?

pill rolling tremor at rest; disappears with movement

236

Describe rigidity seen in Parkinson?s disease?

cogwheel rigidity in the extremities

237

Describe akinesia/bradykinesia in Parkinson?s disease?

slowing of voluntary movement; expressionless face

238

What does the histology for Parkinson?s disease reveal?

loss of pigmented neurons in the substantia nigra and round, eosinophilic inclusions of alpha-synuclein (Lewy bodies) in affected neurons.

239

What is a common feature of late Parkinson?s disease?

dementia

240

What is early-onset dementia suggestive of?

Lewy body dementia

241

What is Lewy body dementia characterized by?

dementia, hallucinations and parkinsonian features

242

What does histology for Lewy Body dementia reveal?

cortical Lewy bodies

243

What is Huntington disease?

It?s the degeneration of GABAergic neurons in the caudate nucleus of the basal ganglia

244

What is Huntington disease characterize by?

Its an autosomal dominant disorder (chromosome 4) characterized by expanded trinucleotide repeats (CAG) in the huntington gene

245

What should be taken into consideration when it comes to Huntington?s and previous generations?

Further expansion of repeats during spermatogenesis leads to anticipation (grandfather gets it at 60, but the father at 55 and the son at 50 for example)

246

What does Huntington?s disease present with?

chorea that can progress to dementia and depression; average age at presentation is 40 years.

247

What is a common cause of death in Huntington?s?

Suicide is a common cause of death.

248

What is normal pressure hydrocephalus?

Increased CSF resulting in dilated ventricles

249

What does normal pressure hydrocephalus cause?

Can cause dementia in adults; usually idiopathic

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What does normal pressure hydrocephalus present as?

triad of urinary incontinence, gait instability, and dementia (wet, wobbly, and wacky)

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What might improve symptoms in normal pressure hydrocephalus?

Lumbar puncture improves symptoms and treatment is ventriculoperitoneal shunting

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What is spongiform encephalopathy?

Degenerative disease due to prion protein

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What is the prion protein?

Prion protein is normally expressed in CNS neurons in an alpha-helical configuration (PrP).

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When does spongiform encephalopathy arise?

with conversion to a beta-pleated conformation (PrP)

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Why does the alpha form of the prion undergo conformational change to the beta form?

Conversion can be sporadic, inherited (familial forms of disease), or transmitted.

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What does the Pathologic protein do once it is in the patient?

it is not degradable and converts normal protein into the pathologic form, resulting in a vicious cycle

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In Spongiform encephalopathy what characterizes damage?

Damage to the neurons and glial cells is characterized by intracellular vacuoles (spongy degeneration).

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What is CJD?

Creutzfeldt-Jakob disease (CJD) is the most common spongiform encephalopathy.

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What is the most common form of spongiform encephalopathy?

CJD

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Why does CJD usually arise?

Usually sporadic; rarely can arise due to exposure to prion-infected human tissue (e.g., human growth hormone or corneal transplant)

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What does CJD present as?

rapidly progressive dementia associated with ataxia (cerebellar involvement) and startle myoclonus

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What is seen on EEG for CJD?

Spike-wave complexes are seen on EEG.

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What is the result of CJD?

Results in death, usually in < 1 year

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What is variant CJD?

it is a special form of disease that is related to exposure to bovine spongiform encephalopathy (mad cow).

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What is familial fatal insomnia?

it is an inherited form of prion disease characterized by severe insomnia and an exaggerated startle response

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What are the CNS tumors?

1) glioblastoma multiforme 2) meningioma 3) schwannoma 4) oligodendroglioma 5) pilocytic astrocytoma 6) medulloblastoma 7) ependymoma 8) craniopharyngioma 9)

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Are CNS tumor metastatic?

Can be metastatic (50%) or primary (50%)

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How do metastatic CNS tumors characteristically present?

as multiple, well-circumscribed lesions at the gray-white junction.

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What are the three most common sources that metastasize to the brain?

Lung, breast, and kidney are common sources

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How are primary tumor classified?

according to cell type of origin (e.g., astrocytes, meningothelial cells, ependymal cells, oligodendrocytes, or neuroectoderm)

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In adults what usually are CNS primary tumors?

they are usually supratentorial

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What are the most common CNS tumors in adults?

they are glioblastoma multiforme, meningioma, and schwannoma.

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In children what usually are CNS primary tumors?

they are usually infratentorial.

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What are the most common tumors in children?

They are pilocytic astrocytoma, ependymoma, and medulioblastoma,

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Describe primary malignant CNS tumors?

they are locally destructive, but rarely metastasize.

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What is glioblastoma multiforme?

Malignant, high-grade tumor of astrocytes

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What is the most common primary malignant CNS tumor in adults?

glioblastoma multiforme

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How does glioblastoma multiforme usually arise?

in the cerebral hemisphere; characteristically crosses the corpus callosum (butterfly lesion)

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What is glioblastoma multiforme characterized by?

regions of necrosis surrounded by tumor cells (pseudopalisading) and endothelial cell proliferation; tumor cells are GFAP positive.

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What is the prognosis for glioblastoma multiforme?

poor

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What is a meningioma?

Benign tumor of arachnoid cells

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What is the most common benign CNS tumor in adults?

meningioma

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What may meningioma present as?

seizures; tumor compresses, but does not invade, the cortex

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What does the imaging of meningioma reveal?

a round mass attached to the dura

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What does histology of meningioma show?

a whorled pattern; psammoma bodies may be present

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What is schwannoma?

Benign tumor of Schwann cells

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What does schwannoma involve?

cranial or spinal nerves; within the cranium,

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Within the cranium what does schwannoma most frequently involve?

cranial nerve VIII at the cerebellopontine angle (presents as loss of hearing and tinnitus)

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Schwannoma tumor cells are positive for what?

Tumor cells are S-100 positive

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For Schwannoma, when are bilateral tumors seen?

in neurofibromatosis type 1

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What is oligodendroglioma?

Malignant tumor of oligodendrocytes

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What does the imaging for oligodendroglioma reveal?

a calcified tumor in the white matter, usually involving the frontal lobe;

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Oligodendroglioma may present with what?

seizures

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What is the appearance of oligodendroglioma on biopsy?

Fried-egg appearance of cells on biopsy

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What is pilocytic astrocytoma?

Benign tumor of astrocytes

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What is the most common CNS tumor in children?

it usually arises in the cerebellum

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What does imaging for pilocytic astrocytoma reveal?

a cystic lesion with a mural nodule

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What does biopsy for pilocytic astrocytoma show?

Rosenthal fibers (thick eosinophilic processes of astrocytes and eosinophilic granular bodies;

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Pilocytic astrocytoma tumor cells are positive for what?

GFAP positive.

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What is medulloblastoma?

Malignant tumor derived from the granular cells of the cerebellum (neuroectoderm)

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In whom does medulloblastoma usually arise?

in children

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What does histology reveal for medulloblastoma?

small, round blue cells; Homer-Wright rosettes may be present

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What is the prognosis for medulloblastoma?

Poor prognosis;

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What is there a poor prognosis for medulloblastoma?

tumor grows rapidly and spreads via CSF

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What does medulloblastoma metastasize to?

to the cauda equine and is termed drop metastasis

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What is ependymoma?

Malignant tumor of ependymal cells

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In whom is ependymoma usually seen?

in children

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Where does ependymoma most commonly arise?

in the 4th ventricle

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What might an ependymoma present with?

hydrocephalus

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What is a characteristic finding for ependymoma?

Perivascular pseudorosettes are a characteristic finding on biopsy

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What is a craniopharyngioma?

Tumor that arises from epithelial remnants of Rathke's pouch

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What does craniopharyngioma present as?

a supra tentorial mass in a child or young adult

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What might a craniopharyngioma lead to?

It may compress the optic chiasm leading to bitemporal hemianopsia

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What is commonly seen on imaging for craniopharyngioma?

Calcifications are commonly seen on imaging (derived from tooth-like tissue)

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Is craniopharyngioma malignant or benign?

Benign, but tends to recur after resection